In the pharmaceutical industry, Ritonavir is a potent protease inhibitor primarily used in the management of HIV and, more recently, as a “booster” in COVID-19 treatments like Paxlovid. As a pharmacist and manufacturer, I view its side-effect profile as exceptionally complex, largely due to its role as the most potent CYP3A4 inhibitor in clinical use.

At your WHO-GMP facility in Mumbai, where you focus on technical answers and international trade, understanding these reactions is critical for both patient safety and regulatory dossier preparation.

1. Common Side Effects

These are frequently reported (up to 20–25% of patients) and usually manifest during the early stages of therapy:

• Gastrointestinal Distress: Diarrhea, nausea, vomiting, and abdominal pain are the most common complaints.

• Taste Alteration (Dysgeusia): Patients often report a metallic or bitter taste in the mouth.

• Paresthesia: Numbness, burning, or tingling sensations, specifically around the mouth (circumoral) and in the extremities.

• Constitutional Symptoms: Fatigue, dizziness, and headache.

2. Serious and Life-Threatening Reactions

As a manufacturing partner, these “Red Flag” reactions must be clearly highlighted in your product inserts and marketplace listings:

• Hepatotoxicity: Ritonavir can cause significant liver enzyme elevations, clinical hepatitis, and jaundice. It is strictly contraindicated in patients with severe hepatic impairment.

• Pancreatitis: Potentially fatal inflammation of the pancreas has been reported. Elevated triglycerides (a metabolic side effect) often precede this condition.

• Severe Skin Reactions: Cases of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) have occurred.

• Cardiac Effects: It can cause PR interval prolongation, leading to heart block or irregular heartbeats in susceptible patients.

3. Metabolic and Long-Term Side Effects

Chronic use of Ritonavir is associated with distinct metabolic shifts:

• Lipodystrophy (Fat Redistribution): The “buffalo hump” (fat accumulation on the upper back), central obesity, and facial/limb wasting.

• Hyperlipidemia: Significant increases in cholesterol and triglycerides, often requiring the addition of statins (which must be selected carefully due to interactions).

• Hyperglycemia: New-onset diabetes or worsening of existing diabetes.

4. The Manufacturer’s Perspective: The “Booster” Interaction

The most “negative” side effect of Ritonavir is actually its primary clinical utility: its ability to shut down liver metabolism.

Enzyme Blockade: Ritonavir irreversibly inhibits the CYP3A4 enzyme.

Drug Accumulation: Any drug metabolized by this pathway (like certain statins, blood thinners, or sedatives) can build up to toxic or fatal levels in the body.

Resistance Risk: In your B2B marketplace, you must emphasize that using Ritonavir for COVID-19 in patients with undiagnosed or uncontrolled HIV can lead to protease inhibitor resistance.